At a Glance

Why Get Tested?

When to Get Tested?

When a bone mineral density scan indicates reduced bone density; before and periodically during treatment for bone loss to evaluate effectiveness, to determine if the rate of loss has decreased or the rate of bone formation has increased

Sample Required?

A blood sample drawn from a vein in your arm or sometimes a urine sample

Test Preparation Needed?

Fasting may be required before testing; samples are typically collected in the morning.

The Test Sample

What is being tested?

Bone is the rigid, hard connective tissue that comprises the majority of the skeleton in humans. It is a living, growing tissue that turns over at a rate of about 10% a year. Bone markers are blood and urine tests that detect products of bone remodeling to help determine if the rate of bone resorption and/or formation is abnormally increased, suggesting a potential bone disorder. The markers can be used to help determine a person's risk of bone fracture and to monitor drug therapy for people receiving treatment for skeletal disorders including osteoporosis.

Bone is made up largely of type-I collagen, a protein network that gives the bone its tensile strength and framework, and calcium phosphate, a mineralized complex that hardens the skeletal framework. This combination of collagen and calcium gives bone its hardness, and yet bones are flexible enough to bear weight and withstand stress. More than 99% of the body's calcium is contained in the bones and teeth. Most of the remaining 1% is found in the blood.

Throughout a person's lifetime, bone is constantly being remodeled to maintain a healthy bone structure that conforms to the person's needs. There are two major types of cells within bone: osteoblasts and osteoclasts. Osteoblasts are the cells that lay down new bone, but they first initiate bone resorption by stimulating osteoclasts, which dissolve small amounts of bone in the area that needs strengthening using acid and enzymes to dissolve the protein network.

Osteoblasts then initiate new bone formation by secreting a variety of compounds that help form a new protein network, which is then mineralized with calcium and phosphate. This on-going remodeling process takes place on a microscopic scale throughout the body to keep bones alive and sturdy.

During early childhood and in the teenage years, new bone is added faster than old bone is removed. As a result, bones become larger, heavier, and denser. Bone formation happens faster than bone resorption until a person reaches their peak bone mass (maximum bone density and strength) between the ages of 25 and 30 years. After this peak period, bone resorption occurs faster than the rate of bone formation, leading to net bone loss. The age at which an individual begins to experience symptoms of bone loss depends on the amount of bone that was developed during their youth and the rate of bone resorption. Traditionally, women exhibit these symptoms earlier than men because they may not have developed as much bone during the peak years and, after menopause, rate of bone loss is accelerated in some women.

Several diseases and conditions can cause an imbalance between bone resorption and formation, and bone markers can be useful in detecting the imbalance and bone loss. Most often, the markers have been studied in the evaluation and monitoring of osteoporosis, including age-related osteoporosis or secondary osteoporosis, which is bone loss due to an underlying condition. Bone loss may result from conditions such as rheumatoid arthritis, hyperparathyroidism, Cushing disease, chronic kidney disease, multiple myeloma, or from prolonged use of drugs such as anti-epileptics, glucocorticoids, or lithium.

Below is a list of some bone resorption and formation markers measured in blood and/or urine samples. Research is ongoing for new biomarkers that can predict abnormal bone loss in various disease states. For many of these markers, caution is required in interpreting test results as they can be affected by diet, exercise, and time of day the sample is collected.

The International Osteoporosis Foundation (IOF) and the International Federation for Clinical Chemistry (IFCC) recommend two blood tests for evaluating bone turnover:

A blood test for C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) as a marker for bone resorption

A blood test for P1NP (Procollagen type 1 N-terminal propeptide) as a marker for bone formation

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

It may be necessary to fast prior to testing. Many of the bone markers vary in the blood and urine depending upon the time of day (diurnal variation), so sample timing can be important. Carefully follow any instructions given for the timing of sample collection, such as collecting a second morning void of urine.

The Test

How is it used?

One or more of the bone marker tests may be used to help determine if a person has increased rates of bone turnover (resorption and/or formation). Bone markers are sometimes used as an adjunct to bone density testing (e.g., BMD, DEXA scan) to help evaluate bone loss and detect some bone diseases. They often are used to monitor response to anti-resorptive therapy for bone disease, primarily osteoporosis, and to help a doctor determine if the dose of the drug a person is receiving is effective.

These tests can detect response to anti-resorption or bone formation therapies in a much shorter time period than the X-ray types of bone density testing (three to six months versus one to two years). This way, therapy can be adjusted or altered in a more timely manner if a person is not responding as expected.

The International Osteoporosis Foundation (IOF) and the International Federation for Clinical Chemistry (IFCC) recommend two blood tests for evaluating bone turnover:

C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker for bone resorption. It is a peptide fragment from the carboxy terminal end of the protein matrix; used to monitor anti-resorptive therapies, such as bisphosphonates and hormone replacement therapy, in postmenopausal women and people with low bone mass (osteopenia)

P1NP (Procollagen type 1 N-terminal propeptide) – a marker for bone formation. It is formed by osteoblasts; reflects rate of collagen and bone formation; may be ordered along with bone resorption marker such as C or N-telopeptide; most sensitive marker of bone formation and particularly useful for monitoring bone formation therapies and anti-resorptive therapies; it is recommended that the test be performed at baseline before starting osteoporosis therapy and again 3 to 6 months later.

Other urine or blood tests used less commonly for bone resorption include:

N-telopeptide (N-terminal telopeptide of type 1 collagen (NTx)) – a peptide fragment from the amino terminal end of the protein matrix; another marker used to monitor therapy.

Pyridinium Crosslinks – a group of collagen breakdown products that includes DPD; used to monitor therapy response; not as specific for bone collagen as the telopeptides.

Tartrate-resistant acid phosphatase (TRAP) is the version of acid phosphatase produced by osteoclasts, the cells that dissolve small amounts of bone, during bone resorption.

Other bone formation blood tests that may sometimes be used include:

Bone-specific alkaline phosphatase (ALP) – one of the isoenzymes (types) of ALP; it is associated with osteoblast cell function, the type of cell involved in bone formation. It is thought to have a role in bone mineralization; it is recommended that the test be performed at baseline before starting osteoporosis therapy and again 3 to 6 months later; results may be affected by the level of liver ALP.

Osteocalcin (bone gla protein) – a protein formed by osteoblasts; part of the non-collagen portion of the bone structure; some of it also enters the bloodstream; the level of osteocalcin in the blood reflects the rate of bone formation, thus it is a useful indicator of the function of osteoblasts. This test may be affected by use of the drug warfarin (Coumadin®).

When is it ordered?

Testing may be performed along with other tests such as a calcium, vitamin D, thyroid testing, and parathyroid hormone when bone loss is detected during a bone mineral density test (diagnostic imaging) and/or when a person has a history of unexpected bone fracture.

One or more bone marker tests may be performed prior to anti-resorptive or bone formation therapy and then typically 3 to 6 months later to monitor the effectiveness of treatment.

What does the test result mean?

A high level of one or more bone markers in urine and/or blood suggests an increased rate of resorption and/or formation of bone, but it does not indicate the cause (it is not diagnostic). An elevated level of bone markers may be seen in conditions such as:

Is there anything else I should know?

Samples must be consistently collected, and test results must be interpreted with caution. There is both day-to-day variability in bone marker concentrations and diurnal variation (changes throughout the day). Most bone marker concentrations will be the highest in the morning, and some, in particular, alkaline phosphatase, are affected by eating.

Most people with bone loss are not aware of it. The condition may not cause any symptoms until a person has an unexpected bone fracture.

Since people with breast or prostate cancer have a high incidence of bone metastases, there is also some evidence that bone markers can help doctors predict which breast and prostate cancer patients may be at a high risk for complications from bone metastases and thus eligible for bone resorption sparing medications such as the bisphosphonates.

There are limitations to the clinical utility of many of these bone markers, but researchers continue to explore ways to improve their clinical use. Their principal use is to gauge the effectiveness of the many therapies used to treat metabolic bone disease and to properly adjust the dose for maximal effect.

1. Should everyone have bone marker testing performed?

Bone marker testing is typically only indicated in those who have been diagnosed with or are at risk of bone loss. The tests are not intended to be used to screen the general public. They offer additional information to the doctor but do not take the place of bone mineral density screening.

2. Will I have all or just some of these bone markers tested?

Typically, no one will have all of the tests done that are described here. Most doctors use one or a few particular bone markers, including one or two that evaluate bone resorption and one or two that evaluate bone formation. The choice of bone markers will depend on many factors, including your medical history, signs and symptoms, and physical examination, and these all vary from person to person. Your doctor will make the selection based on the usefulness of the tests for your condition. In general, if a test is ordered as a baseline prior to therapy, then the same test will be ordered later so that the two results can be compared.

3. Can testing be performed in my doctor's office?

In general, no. While a blood or urine sample may be collected in your doctor's office, the sample will be sent to a laboratory for testing. Bone marker testing is not offered by all laboratories and will often be sent to a reference laboratory.

4. What can I do to increase or decrease bone marker results?

People can and should take steps to maintain bone health throughout their life, but bone markers themselves are not affected by lifestyle changes. If you have bone loss, work with your healthcare practioner to determine the best treatment for you.

Article Sources

NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Interview with Laurence M. Demers, PhD. Distinguished Professor of Pathology and Medicine, The Pennsylvania State University College of Medicine, The M. S. Hershey Medical Center, Hershey, PA. Additionally, conducted article review March 2009.

Srivastava, A. (2005 July 22). Clinical Use of Serum and Urine Bone Markers in the Management of Osteoporosis. Medscape from Curr Med Res Opin 2005;21(7): 1015-1026 [On-line journal]. Available online at http://www.medscape.com/viewarticle/508542_print through http://www.medscape.com.

Hyperparathyroidism: What It Is and How It's Treated (July 2006-Online information). American Association of Family Physicians. Available online at http://familydoctor.org/251.xml through http://familydoctor.org.

Centers for Disease Control and Prevention. Improving the Clinical Use of Biochemical Bone Marker in Metabolic Bone Diseases. Available online at http://www.cdc.gov/NCEH/DLS/osteoporosis.htm through http://www.cdc.gov. Accessed March 2009.

Srivastava, A. (2005 July 22). Clinical Use of Serum and Urine Bone Markers in the Management of Osteoporosis. Medscape Current Medical Research and Opinion [On-line information]. Available online at http://www.medscape.com/viewarticle/508542 through http://www.medscape.com.

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This article was last reviewed on May 14, 2013. | This article was last modified on May 14, 2013.

The review date indicates when the article was last reviewed from beginning to end to ensure that it reflects the most current science. A review may not require any modifications to the article, so the two dates may not always agree.

The modified date indicates that one or more changes were made to the article. Such changes may or may not result from a full review of the article, so the two dates may not always agree.